1. Field of the Invention
The present invention relates to cosmetic or dermatologic compositions and to the use of such compositions for depigmenting and/or lightening the skin, body hair and/or head hair. The present invention also relates to methods for the manufacture of compositions useful for depigmenting and/or lightening the skin body hair, and/or head hair.
2. Discussion of the Background
At various times in their life, some people experience the appearance, on the skin and more especially on the hands, of darker and/or more highly colored spots, which confer heterogeneity on the skin. These spots are due to a high concentration of melanin in the keratinocytes situated at the surface of the skin. Indeed, the melanocytes situated in the basal portion of the epidermis produce melanin and deliver this melanin to the surrounding keratinocytes, which then rise to the surface of the epidermis, charged with melanin.
The mechanism for the formation of the pigmentation of the skin, that is to say the formation of melanin, is particularly complex and schematically involves the following main steps:Tyrosine→Dopa→Dopaquinone→Dopachrome→Melanin
Tyrosinase is the main enzyme involved in this sequence of reactions. It catalyzes in particular the reaction for converting tyrosine to Dopa (dihydroxyphenylalanine) and the reaction for converting the Dopa to dopaquinone. This tyrosinase acts only when it is in the state of maturation under the action of certain biological factors.
A substance is recognized as being depigmenting if it acts directly on the vitality of the epidermal melanocytes where melanogenesis occurs and/or if it interferes with one of the steps in the biosynthesis of melanin either by inhibiting one of the enzymes involved in melanogenesis or by being involved as a structural analogue of one of the chemical compounds in the chain for the synthesis of melanin, which chain may then be blocked and thus bring about depigmentation.
The substances most widely used as depigmenting agents are more particularly hydroquinone and its derivatives, in particular its ethers such as hydroquinone monomethyl ether and monoethyl ether. Although they are definitely effective, these compounds are unfortunately not free of side effects because of their toxicity, which can make their use delicate, or even dangerous. This toxicity comes from the fact that they act on the basic mechanisms of melanogenesis by killing cells which then risk disrupting their biological environment and which consequently force the skin to delete them by producing toxins.
Thus, hydroquinone, whose use is in fact legally limited in Europe to a concentration of 2%, is a compound which is particularly irritating and cytotoxic for the melanocyte, whose complete or partial replacement has been envisaged by many authors.
The use of harmless topical depigmenting substances having a high efficacy is most particularly sought for the treatment of regional hyperpigmentations caused by melanocyte hyperactivity, such as idiopathic melasmas, occurring during pregnancy (“mask of pregnancy” or chloasma), or oestroprogestrogen contraception, localized hyperpigmentations caused by benign melanocyte hyperactivity and proliferation, such as senile pigmented spots called actinic lentigo, accidental hyperpigmentations such as photosensitization and post-lesion cicatrization, as well as certain leukodermas such as vitiligo. For the latter hyperpigmentations, short of being able to repigment the damaged skin, depigmentation of the areas of residual normal skin is completed in order to give the whole skin a homogeneous light complexion.
Thus, substances have been sought which are not involved in the mechanism of melanogenesis but which, instead, act upstream on tyrosinase by preventing its activation and are consequently a lot less toxic.
Various depigmenting agents have thus been proposed. In particular, it has been demonstrated that certain aminophenol derivatives have the property of inhibiting melanogenesis even in low concentrations, without demonstrating cytotoxicity. These compounds, which are described in International PCT Patent Application No. WO 99/10318, (U.S. patent application Ser. No. 09/284,490 filed Jun. 21, 1999), comprise in particular N-cholesteryloxycarbonyl-4-para-aminophenol.